Modeling angiogenesis in the human brain in a tissue-engineered post-capillary venule.

Angiogenesis plays an essential role in embryonic development, organ remodeling, wound healing, and is also associated with many human diseases. The process of angiogenesis in the brain during development is well characterized in animal models, but little is known about the process in the mature brain. Here, we use a tissue-engineered post-capillary venule (PCV) model incorporating stem cell derived induced brain microvascular endothelial-like cells (iBMECs) and pericyte-like cells (iPCs) to visualize the dynamics of angiogenesis. We compare angiogenesis under two conditions: in response to perfusion of growth factors and in the presence of an external concentration gradient. We show that both iBMECs and iPCs can serve as tip cells leading angiogenic sprouts. More importantly, the growth rate for iPC-led sprouts is about twofold higher than for iBMEC-led sprouts. Under a concentration gradient, angiogenic sprouts show a small directional bias toward the high growth factor concentration. Overall, pericytes exhibited a broad range of behavior, including maintaining quiescence, co-migrating with endothelial cells in sprouts, or leading sprout growth as tip cells.

Tissue-Engineered Microvessels: A Review of Current Engineering Strategies and Applications.

Microvessels, including arterioles, capillaries, and venules, play an important role in regulating blood flow, enabling nutrient and waste exchange, and facilitating immune surveillance. Due to their important roles in maintaining normal function in human tissues, a substantial effort has been devoted to developing tissue-engineered models to study endothelium-related biology and pathology. Various engineering strategies have been developed to recapitulate the structural, cellular, and molecular hallmarks of native human microvessels in vitro. In this review, recent progress in engineering approaches, key components, and culture platforms for tissue-engineered human microvessel models is summarized. Then, tissue-specific models, and the major applications of tissue-engineered microvessels in development, disease modeling, drug screening and delivery, and vascularization in tissue engineering, are reviewed. Finally, future research directions for the field are discussed.